First Analysis of the New FDA Draft on Aseptic Processing

GMP News No. 255

GMP News
28 October 2002

FirstAnalysis of the New FDA Draft
on Aseptic Processing

For many years, the pharmaceutical industry has been waiting for the newFDA "Guideline On Sterile Drug Products Produced By AsepticProcessing." In the meantime, a non-authorised version has beencirculating through the pharmaceutical industry since 1998.

At the end of September 2002, FDA finally published an officialPreliminary Concept Paper with the title "Sterile Drug Products Produced By AsepticProcessing" as Draft for commenting by the industry.

The document is subdivided into 12 chapters:

  • Introduction
  • Background
  • Scope
  • Buildings and Facilities
  • Personnel Training, Qualification, & Monitoring
  • Components and Containers/Closures
  • Endotoxin Control
  • Time Limitations
  • Process Validation and Equipment Qualification
  • Laboratory Controls
  • Sterility Testing
  • Batch Record Review: Process Control Documentation

In addition, at the end of the document you will find the 3 appendices:

  • Aseptic Processing Isolators
  • Blow-Fill-Seal Technology
  • Processing Prior To Filling/Sealing Operations

as well as the points References, Relevant Guidance Documents and DraftGlossary.

On the whole, one can say that - in comparison with the currentGuideline - FDA has included topical subjects as well as much-discussedtopics of aseptic production. The main chapters of the Guideline are "Process Validation"and "Laboratory Controls" with the subchapter "Environmental Monitoring."Besides, the isolator and blow-fill-seal technologies have found their wayinto the Guideline.

As an example, here some notes on "Environmental Monitoring."On the whole, the environmental monitoring programme is assigned a centralrole. Monitoring data are meant to serve both as quality information onthe batch and as trend data for the production environment.

The chapter is subdivided into the 4 subchapters:

  • General Written Programme
  • Establishing Limits and a Trending Programme
  • Sanitisation Efficacy
  • Monitoring Methods

The "General Written Program" regulates the points: samplinglocation,frequency of sampling,when the samples are taken,durationof sampling,sample size, specificsampling equipment and techniques,alert andaction limits, appropriateresponse to deviations from alert or action limits.

As to the limits and trending programme, importance is given tothe individual results. The calculation of mean values is considered ascritical. Trending is to be divided into near-term and long-term trends.Whenever a result is at the alert or action limit, measures have to betaken. In case atypical microorganisms (which ones?) are detected, furtherinvestigations have to be conducted. The responsible managers have to beinformed regularly about trends and investigations.

As regards sanitisation efficacy, the document requires that thesporicidal efficacy of disinfectants is proved and that these agents areapplied regularly. Another requirement is that sanitisation efficacy isproved regularly within the framework of the monitoring programme.

Under "Monitoring Methods" you can find surface monitoring aswell as active and passive air monitoring. The efficacy of passivemonitoring by means of petri dishes has to be proved (effect of thedesiccation of the plates on the recovery rate of microorganisms).

Surely, some of the requirements, especially in the chapter"Environmental Monitoring", may (by far) overshoot the mark andgive rise to uncertainty. This is one of the reasons why thepharmaceutical industry should take this Draft seriously and seize theopportunity to make contributions to the incipient discussion.

Dr Andreas Mangel


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